Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

Jason E. Farrar, Paola Quarello, Ross Fisher, Kelly A. O'Brien, Anna Aspesi, Sara Parrella, Adrianna L. Henson, Nancy E. Seidel, Eva Atsidaftos, Supraja Prakash, Shahla Bari, Emanuela Garelli, Robert J. Arceci, Irma Dianzani, Ugo Ramenghi, Adrianna Vlachos, Jeffrey M. Lipton, David M. Bodine, Steven R. Ellis

Research output: Contribution to journalArticlepeer-review


Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalAmerican journal of hematology
Issue number10
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Hematology

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